Responding to the concern that various viruses, bacteria, and bacterial toxins could be used as bioterrorist weapons, we are proposing to develop a transdermal vaccine delivery platform that can be administered by untrained end users in any place and at any time to protect civilian as well as military populations. The proposed vaccine delivery method will be needle-free, minimally invasive, inexpensive, easy to store and transport, and better tolerated by the human body. Most importantly, it will provide enhanced immunogenicity. While humoral immunity is essential for the control of extracellular pathogens, cell-mediated immunity is vital for host defense against intracellular pathogens, including viruses. Cell-mediated immunity, associated with the activation of CD8 cytotoxic T lymphocytes, is effectively administered through the pathway involving a special subpopulation of antigen-presenting cells, such as Langerhans cells (LCs). The epidermal layer of human skin, about 20 mu/m below the skin surface and about 100-200 (m thick, is highly immunoreactive because it contains abundant Langerhans cells, and is therefore an ideal target for vaccine injection. However, because the epidermal layer is thin and near the skin surface, it is difficult to inject target vaccine into the epidermal layer with the conventional needle injection method. Our strategy is to use a microneedle array, each needle about 300 pm in length, to perforate the stratum corneum and deliver vaccine in proximity to Langerhans cells in the epidermis. We hypothesize that the micro-needle vaccine injection may deliver vaccines to the cytosol of the Langerhans cells and induce a cytotoxic T lymphocyte response. Specific aims of this R21 study are to (1) develop an influenza vaccine micro-needle array and (2) evaluate vaccine delivery in mouse models.